Targeting the tumor immune microenvironment: GPCRs as key regulators in triple-negative breast cancer

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its aggressive nature and limited therapeutic options. Recent research underscores the pivotal role of G protein-coupled receptors (GPCRs) in shaping the tumor immune microenvironment (TIME) within TNBC. This review focuses on four principal GPCRs-chemokine receptors, sphingosine-1-phosphate receptors, prostaglandin E2 receptors, and lactate receptors-that have garnered substantial attention in TNBC studies. GPCRs modulate immune cell recruitment, polarization, and function, thereby fostering an immunosuppressive milieu conducive to tumor progression and metastasis. The review examines how alterations in GPCR expression on immune cells influence the pathogenesis and advancement of TNBC. Further, it discusses emerging therapeutic strategies targeting GPCR signaling pathways to remodel the immunosuppressive TIME in TNBC. These insights into GPCR-mediated immune regulation not only deepen our comprehension of TNBC's pathophysiology but also offer promising avenues for developing novel immunotherapies aimed at enhancing clinical outcomes for TNBC patients.